During the process of metastasis development, it is known that a cancer cell which has strayed into a blood vessel or lymphoduct adheres to an endothelial cell or to its extracellular matrix (so-called basement membrane) and the thus adhered cancer cell permeates into the extra-cellular matrix to develop a new metastatic lesion in the tissue. For example, S. Korach et al. (Cancer Research, 46, 3624-3629, 1986) reported that they have divided cancer cells into a high metastatic group and a low metastatic group and through their cancer cell cloning studies, conducted in vitro adhesion tests of cancer cells to cultured endothelial. As a result, the adhesiveness of cancer cells to blood vessel endothelial cells or to their extra-cellular matrices is closely related to metastasis of cancer cells because the high metastatic group cancer cells showed a high adhesiveness while the low metastatic cells showed a low adhesiveness.
On the other hand, the peptide sequence GRGDS (Gly-Arg-Gly-Asp-Ser) of the cell adhesion moiety of fibronectin which is a component of the extra-cellular matrix, competitively inhibits binding between cancer cells and the extra-cellular matrix. Yamada et al. (Science, 233, 467-470, 1986) reported that the peptide GRGDS inhibited lung metastasis of B16F10 cells in mice. These results indicate that a substance which has cell adhesion inhibitory activity in a small amount could be used as a metastasis inhibitor.
The present invention has been accomplished based on a finding that certain types of phospholipid-or lipid-linked glycosaminoglycans can inhibit adhesion of cancer cells to blood vessel endothelial cells and their extra-cellular matrices and, as a result, can inhibit metastasis of cancer cells.